Login / Signup

USP15 Deubiquitinates CARD9 to Downregulate C-Type Lectin Receptor-Mediated Signaling.

Wenting XuJason S RushDaniel B GrahamZhifang CaoRamnik J Xavier
Published in: ImmunoHorizons (2020)
Posttranslational modifications are efficient means to rapidly regulate protein function in response to a stimulus. Although ubiquitination events and the E3 ubiquitin ligases involved are increasingly characterized in many signaling pathways, their regulation by deubiquitinating enzymes remains less understood. The C-type lectin receptor (CLR) signaling adaptor CARD9 was previously reported to be activated via TRIM62-mediated ubiquitination. In this study, we identify the deubiquitinase USP15 as a novel regulator of CARD9, demonstrating that USP15 constitutively associates with CARD9 and removes TRIM62-deposited ubiquitin marks. Furthermore, USP15 knockdown and knockout specifically enhance CARD9-dependent CLR signaling in both mouse and human immune cells. Altogether, our study identifies a novel regulator of innate immune signaling and provides a blueprint for the identification of additional deubiquitinases that are likely to control these processes.
Keyphrases
  • innate immune
  • signaling pathway
  • transcription factor
  • genome wide
  • dna methylation
  • protein protein
  • binding protein
  • amino acid